Scientists believe that some risk factors, such as the use of tobacco or alcohol, may cause esophageal cancer by damaging the DNA in cells that line the inside of the esophagus. Long-term irritation of the lining of the esophagus, as happens with reflux, Barrett’s esophagus, achalasia, Plummer-Vinson syndrome, or scarring from swallowing lye, may also lead to DNA damage.

DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look. Some genes control when cells grow, divide into new cells, and die. Genes that help cells grow, divide, and stay alive are called oncogenes. Genes that slow down cell division or make cells die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

The DNA of esophageal cancer cells often shows changes in many different genes. However, it’s not clear if there are specific gene changes that can be found in all (or most) esophageal cancers.

Some people inherit DNA changes (mutations) from their parents that increase their risk for developing certain cancers. But esophageal cancer does not seem to run in families, and inherited gene mutations are not thought to be a major cause of this disease.